JP2010500559A - Nanowire sensor, nanowire sensor array, and method of forming the sensor and sensor array - Google Patents

Abstract

A method of forming a sensor comprising nanowires on a support substrate, wherein the first semiconductor layer is disposed on the support substrate is disclosed. The method includes the step of forming a fin structure comprising a first semiconductor layer and including at least two support portions and a fin portion disposed between the support portions; and oxidizing at least the fin portion of the fin structure; Forming a nanowire surrounded by the first oxide film layer; and forming an insulating layer on the supporting portion, wherein the supporting portion and the first insulating layer constitute a microfluidic channel. Nanowire sensors are also disclosed. A nanowire sensor includes: a support substrate; a semiconductor fin structure disposed on the support substrate and including at least two semiconductor support portions and a fin portion disposed between the support portions; and a contact surface of the support portion And the support and the first insulating layer constitute a microfluidic channel.

Description

  The present invention relates to the field of sensors, and more particularly to a method of forming a sensor comprising nanowires on a support substrate and a semiconductor layer disposed on the support substrate. The invention further relates to nanowire sensors and nanowire sensor arrays.

One-dimensional nanostructures such as nanowires and carbon nanotubes are recognized as promising candidates for very sensitive ultra-miniaturized molecular sensors. Specifically, sensors utilizing semiconductor nanostructures, such as carbon nanotubes, silicon (Si) nanowires, tin oxide (SnO ₂ ) nanowires, and indium oxide (In ₂ O ₃ ) nanowires, have molecular species in detection by the sensor. This is particularly promising because it utilizes the principle of surface charge change in nanostructures in the presence of or in the absence of molecular species.

  The large surface-to-volume ratio of the nanowire allows the single molecule to be detected because the conductivity of the nanowire varies greatly depending on the surface-attached species. However, most of the existing work that utilizes “bottom-up” nanostructures is a complex that requires the movement and positioning of individual nanostructures to increase the reliability of ohmic contacts and the reliability of doping concentration control. Limited by integration. Furthermore, the delivery of biological receptors such as enzymes, antibodies, proteins, or biopolymers that can be used for analyte detection remains a difficult solution in nanostructured sensor devices. The same challenge applies to the delivery of analytes to be detected. Currently, delivery is usually performed by using a syringe pump, micropipette, or atomic force microscope (AFM) tip tip (dip pen), which can be used to accurately and accurately position the nanowire. Therefore, it becomes a trial and error work that requires a long time with low accuracy. Therefore, such a delivery method can be used only for laboratory experiments, and is not useful from the viewpoint of product realization.

  Several attempts have been made to solve these problems and attempt to enable detection in a flowing environment by utilizing nanowires. Among these attempts, there are biosensors equipped with functions for surface modification, immobilization, detection, and inspection by supplying various fluids. One approach is described in US Pat. The application includes a nanoscale device for detecting the presence or absence of an analyte suspected of being included in a sample by having a sample exposed region, and a nanowire or functionalized nanowire, and a method of using the device It is disclosed. In Patent Document 1, the nanowire functions as a sensor, and a characteristic change can occur when the nanowire comes into contact with a sample suspected of containing an analyte. According to this patent application, nanowires are formed by catalytic vapor deposition (CVD) catalyzed by metallization and catalytic thin film growth by laser deposition.

  In Patent Document 1, the sample exposure region can be any region that is very close to the nanowire, in which case the sample in the sample exposure region acts on at least a portion of the nanowire. An example of a sample exposed area is a fluid flow channel, which can be formed by applying a polydimethylsiloxane (PDMS) solution to a mold. Channels can be created and attached to the surface, and the mold can be removed. Alternatively, the channel can be formed by fabricating the master model using photolithography and pouring PDMS into the master model. The nanowires and fluid channels are formed separately before being incorporated together in the same device by the method described above.

  Another approach is described in US Pat. This application discloses a microscale biosensor used for the detection of target biological material including molecules and cells. A biosensor is a microfluidic system with integrated electronic functions, inflow-outflow ports, and interface structure, pathogen-specific sensitive detection capabilities, and allows processing of biomaterials at the semiconductor interface. Specifically, the biosensor has a detection chamber, the detection chamber is a microwell or microcavity, the microwell or microcavity is formed in the wafer by microfabrication technology, and the microwell or microcavity is targeted A sensing element, such as an electrode, is provided that detects changes in electrical properties or electrical parameters (such as resistance or phase) in the chamber due to the presence of microbial species. In order to perform the detection, in Patent Document 2, integrated metal electrodes are used, and these metal electrodes operate based on the principle of impedance measurement. In order to fabricate a sensor, in Patent Document 2, an integrated metal electrode is formed using top-side processing. The fluid channel is formed in Si using anisotropic etching with potassium hydroxide (KOH) solution. The sensor is believed to be effective for detecting microbial material in the form of pathogenic bacteria having dimensions of about 2 micrometers.

US Patent Application Publication No. 2002/0117659 US Patent Application Publication No. 2001/0053535

  Fabricating the devices according to the prior art described above is very cumbersome and expensive. Accordingly, it is an object of the present invention to provide an easy and low cost sensor that replaces a conventional sensor that advantageously avoids or mitigates some of the aforementioned deficiencies in prior art devices.

  The present invention provides a method for forming a sensor comprising nanowires on a support substrate, wherein the first semiconductor layer is disposed on the support substrate. The method of the present invention comprises the step of forming a fin structure comprising a first semiconductor layer and including at least two support portions and a fin portion disposed between the support portions; Forming a nanowire surrounded by a first oxide film layer by oxidizing the fin portion; and forming a first insulating layer on the support portion; the support portion and the first insulating layer include: Configure the microfluidic channel. The method of the present invention can be a simple and cost-effective method of forming a sensor, but this allows the method of the present invention to be fully compatible with conventional Si (CMOS) technology and is standard. This is because it can be executed in the Si-related manufacturing facility. This means that signal processing can be performed by forming other CMOS circuits together, so that the scale can be reduced and the production cost can be reduced.

  This type of nanowire, which is compatible with CMOS, has been published by Ajay Agalwal et al., Published by IEEE Conference on Emergence Technologies-Nanoelectronics, in the publication entitled "Transport characteristics of Si nanowires in bulk silicon and SOI wafers" N. published in Technologies-Nanoelectronics. Singh et al. Discloses in a publication entitled “Room Temperature Coulomb Blockade Oscillation in Silicon Nanowire n-MOSFETs Fully Surrounded by Gates”. A publication entitled “Transportation Properties of Si Nanowires in Bulk Silicon and SOI Wafers” discloses a method of forming n-type silicon nanowires on bulk and SOI wafers using standard CMOS-compatible techniques, and The publication suggests that nanowires can be integrated with microfluidic channels and applied to biomolecule detection.

  Another type of nanowire that is compatible with CMOS is disclosed in a publication entitled “Room Temperature Coulomb Blockade Oscillation in Silicon Nanowire n-MOSFETs Fully Enclosed by Gates”. This publication describes a full CMOS compatible manufacturing method in which a silicon nanowire NMOS completely surrounded by a gate is formed on a semiconductor on insulator (SOI) wafer.

  In one embodiment of the present invention, the method of the present invention further includes forming a second oxide film layer on the contact surface of the support before forming the first insulating layer. The second oxide film layer is usually silicon oxide, but is not limited to silicon oxide. The second oxide layer can be about 0.2 microns to about 1 micron thick and is thicker than the first oxide layer surrounding the nanowire. The second oxide layer acts to protect the support for subsequent deposition processes.

In another embodiment of the present invention, the method of the present invention further comprises the step of forming a first conductive layer on the contact surface of the second oxide layer before forming the first insulating layer including the fluid channel. Including.
In yet another embodiment of the present invention, the method further includes planarizing the first insulating layer and removing a portion of the first insulating layer to form a portion of the microfluidic channel. Thereby enabling a treatment on the contact surface of the first oxide layer surrounding the nanowire. Examples of the first insulating layer include, but are not limited to, silicon oxide, any other dielectric material, or, for example, SU8, polydimethylsiloxane (PDMS), acetate, Riston, Kapton, Mention may be made of polymers such as polyimide and polyester. In the step of removing a part of the first insulating layer, for example, but not limited to, the etching is selectively performed or dissolved in a chemical such as a developer. The method of the present invention further includes removing the first oxide layer surrounding the nanowire to expose the nanowire and closing the microfluidic channel with a cap layer.

  In another embodiment of the present invention, the method of the present invention further comprises doping the fin with at least one dopant. The at least one dopant can be either p-type or n-type. Examples of p-type dopants include, but are not limited to, boron, aluminum, gallium, and indium, and examples of n-type dopants include, but are not limited to, phosphorus and arsenic. it can. An n-type nanowire can be obtained by doping the fin portion with an n-type dopant, and a p-type nanowire can be formed by doping the fin portion with a p-type dopant. A nanowire having a P / N diode junction is obtained by doping a composite portion consisting of a p-type dopant and an n-type dopant into individual portions of the fin portion. Different nanowire sensors obtained as a result of doping nanowires with different dopants can be used for different applications. The P-type nanowire sensor and the N-type nanowire sensor are complementary to each other. When a specific species acts to increase the conductivity of a P-type nanowire when in contact with the nanowire, the species acts to reduce the conductivity of the N-type nanowire. This will suggest that the signal is authentic and not noise. Further, in order to facilitate signal processing, it is necessary to increase or decrease the conductivity. This increase / decrease changes one of the two conductivity type nanowire sensors to a biological species or biological sample. This is realized by using for a specific charge. In addition, temperature changes can be measured locally at the location of biological activity or biological reaction using a P / N diode junction nanowire sensor.

  In another embodiment of the present invention, the method of the present invention further includes forming a gap in the fin portion by removing a portion of the fin portion. In another embodiment of the present invention, the method further includes the steps of coating a portion of the fin portion with a dielectric material and performing a silicidation process on the fin portion. By performing these steps, nanowires of different conductivity types can be provided in the sensor by the method of the present invention. Examples of these nanowires in the sensor can include silicon nanowires with gaps and silicidated nanowires with gaps. These are also referred to as nano-gap types of sensors. If the nanowire sensor includes a silicon nanowire with a gap, this means that a nanogap can be provided between the two silicon electrodes. If the nanowire sensor includes a silicided nanowire with a gap, a semiconductor portion that functions as a gap can be provided between the two metal electrodes. Any molecule that has a conductivity higher than the gap can be detected by shorting the two electrodes in this case. This detection operation can be expressed as an off mode or an on mode. Silicided nanogap sensors can also be used in biological analysis to record or detect local temperatures, since the sensors are in an anti-parallel diode configuration.

  In another embodiment of the present invention, the second insulating layer is disposed between the support substrate and the first semiconductor layer. As a result, an SOI structure can be obtained because the SOI structure can be constituted by a structure in which the insulating layer is disposed between the support substrate and the first semiconductor layer. The support substrate can include, but is not limited to, silicon, sapphire, polysilicon, silicon oxide, and silicon nitride. The first semiconductor layer can include a material selected from the group consisting of, but not limited to, silicon, gallium arsenide, and silicon-germanium. The second insulating layer can include, but is not limited to, silicon oxide, polymer, and dielectric material.

  In another embodiment of the present invention, the method of the present invention further includes the step of forming at least two openings in the cap layer, each opening of the cap layer being located at a distance away from each support. To do. The method of the present invention further includes forming an electrical connection from each opening to the contact surface of the support by filling each opening with a first conductive layer.

In another embodiment of the invention, the method of the invention further includes oxidizing the entire fin structure. Thereby, the first oxide film layer is formed around the support portion.
In another embodiment of the invention, the method of the invention further comprises depositing a second semiconductor layer on the support substrate prior to depositing the first semiconductor layer. Next, an electrode composed of a second semiconductor layer is formed, and the electrode is located under the nanowire. The method of the present invention further includes depositing a third insulating layer on the electrode prior to forming the fin structure. The second semiconductor layer can include, but is not limited to, silicon, gallium arsenide, and silicon-germanium. The third insulating layer can include, but is not limited to, silicon oxide or a dielectric material.

  In another embodiment of the present invention, the method of the present invention further includes forming a passivation layer on the first conductive layer prior to forming the first insulating layer. The passivation layer can include, but is not limited to, silicon nitride, silicon oxide, or aluminum oxide.

  The present invention further provides a nanowire sensor, the nanowire sensor comprising a support substrate and a semiconductor fin structure disposed on the support substrate. The fin structure includes at least two semiconductor supports and nanowires disposed between the supports; and a first insulating layer over the contact surface of the support. The support portion and the first insulating layer constitute a microfluidic channel.

In one embodiment of the nanowire sensor, the nanowire sensor further comprises a first oxide layer on the contact surface of the support and between the contact surface of the support and the insulating layer.
In another embodiment of the nanowire sensor, the nanowire sensor further comprises a first conductive layer on the contact surface of the first oxide layer and between the contact surface of the first oxide layer and the insulating layer.

  In another embodiment of the nanowire sensor, the nanowire is located on a support substrate, which allows a specimen to contact the entire nanowire and the entire surface because there is a space between the fins and the support substrate. It means that it is possible. Alternatively, the nanowires can be placed directly on the support substrate.

  In another embodiment of the nanowire sensor, the nanowire is composed of an n-type dopant or a p-type dopant. Nanowires can also be formed as P / N diode junctions. As described above, an n-type nanowire can be obtained by doping the nanowire with an n-type dopant, and a p-type nanowire can be formed by doping the nanowire with a p-type dopant. Doping a composite portion consisting of a p-type dopant and an n-type dopant into individual portions of the nanowire results in a nanowire having a P / N diode junction.

In another embodiment of the nanowire sensor, the nanowire includes a gap.
In another embodiment of the nanowire sensor, the nanowire is silicided.
In another embodiment of the nanowire sensor, at least the surface of the nanowire is adapted to bind a capture molecule to the surface, the capture molecule can bind to the analyte of interest and form a complex with the analyte of interest. it can. The analyte of interest can be any chemical or biological compound that contains or can produce a binding partner. Examples of biopolymers that can be detected using nanowire sensors (with or without capture molecules) include, but are not limited to, deoxyribonucleic acid (DNA) molecules, ribonucleic acid (RNA ) Molecules, peptide nucleic acids (PNA), cDNA molecules, or very short oligonucleotides containing for example 10-50 base pairs (bp). The nucleic acid to be detected can be double-stranded, but can also have at least a single-stranded region, or as a single strand for detection of the nucleic acid, for example, previous heat denaturation (strand separation) Exist as a result of In this regard, the sequence of the nucleic acid to be detected can be determined in advance at least in part or all, ie known. Other biopolymers that can be detected using the sensors of the present invention are proteins, peptides, or carbohydrate molecules. Proteins can be composed of 20 amino acids that are observed in proteins in the usual way, but proteins can also contain non-naturally occurring amino acids, for example modified with sugar residues (oligosaccharides) Can be included, or can include post-translational modifications. Furthermore, complexes composed of several different biopolymers such as complexes composed of nucleic acids and proteins can also be detected. Marker proteins suggesting physiological conditions such as cardiac troponin I or T, which are specific markers of myocardial infarction, as illustrative examples of proteins or peptides (the present invention is of course limited to these examples at this point) Or a natriuretic peptide such as brain natriuretic peptide (BNP), which can be used as a marker for diagnosing acute coronary syndrome or acute stroke. Other examples of specimens include human immunodeficiency virus, hepatitis virus (eg, hepatitis A virus, hepatitis B virus, or hepatitis C virus), viruses such as dengue virus, or any living cell ( For example, living organisms such as mammalian cells, bacterial cells), or small organic molecules such as drug candidates, or environmental toxins such as dioxin or DDT can be cited as just a few examples of many analytes of interest. . Appropriate capture molecules are selected depending on the analyte, and the presence or absence or condition of the analyte will be examined. For example, if the analyte is a nucleic acid, the capture molecule can be a nucleic acid molecule, such as, but not limited to, a short oligonucleotide containing about 10-50 base pairs (bp). The oligonucleotide can comprise a sequence portion that is largely complementary to or completely complementary to the nucleic acid to be detected. If the analyte is a protein, organism, or small organic molecule, the capture molecule is an immunoglobulin, such as an antibody (monoclonal or polyclonal), or a fragment thereof that has specific binding affinity for a given analyte itself. possible. Alternatively, the capture molecule may have a specific binding affinity with a labeling substance attached to the analyte. For example, an analyte such as a protein can be labeled with a commonly used labeling group such as digoxigenin or biotin and the capture molecule can be an antibody that binds specifically to digoxigenin, or streptavidin, or It can be a protein such as avidin that specifically binds to biotin. The selection of the corresponding capture molecule is made within the knowledge of a person skilled in the art having ordinary skill in the art.

The surface of the nanowire can be modified, for example, by plasma etching as described in International Patent Application No. WO2005 / 066343 to make the surface suitable for bonding. In the case of nucleic acid molecules, either the nucleic acid molecule to be detected or the capture molecule can be immobilized after plasma etching (see International Patent Application No. WO 2005/066343). In the first case, no capture molecules are required. In another approach to modifying the surface of the nanowire, if such modification is necessary for immobilization of the capture molecule, the surface is silanized with a silane compound having a reactive group such as an epoxy group or an amine group, Through this reactive group, a covalent bond with the corresponding group (eg activated carboxyl group, hydroxyl group, or thiol group) can be induced. A suitable silane molecule is preferably an alkylsilyl compound represented by the general chemical formula X— (CH ₂ ) _p —SiR ₁ R ₂ R ₃ (I), where p is an integer of 1 to 20 And is preferably 1-10, X is a reactive linking group such as NH ₂ or epoxide, and the silane molecule is attached to the surface of the nanowire on the residues R ₁ , R ₂ , and R ₃ . Fixed by at least one of the residues, each of which can independently be hydrogen, halogen, OR ′, NHR ′, NR′R ″, and R ′ and R ″ are alkyl. (Normally, methyl, ethyl, propyl, butyl, etc., preferably n = 0-5, particularly preferably n = 0-2). Compounds such as these are commercially available, for example from ABCR / Gelest (simpler compounds are also commercially available from Fluka or Aldrich). These compounds are particularly advantageous when using silicon-based nanowires. In this case, a covalent bond is formed between the silane molecules via free hydroxy groups on the surface of the nanowire. Other exemplary examples of suitable silane compounds include (3-aminopropyl) trimethoxysilane-tetramethoxysilane (APTMS) or (3-aminopropyl) triethoxysilane-tetramethoxysilane as just a few examples. be able to. A corresponding approach using APTMS silanization is described in a paper entitled “Immobilization of oligonucleotides to silicon surfaces” by Di Pietro et al., Published in Pharmaceutical Discovery, Oct 1, 2005. The technique of modifying the nanowire surface with such a silane compound is also suitable for a method of immobilizing a capture molecule such as an antibody to a small ligand such as biotin on the antibody. For example, a silane compound having an epoxide group first reacts with an N-hydroxysuccinimide (NHS) activated bifunctional ester, which is then converted via conventional linkage (eg, using carbodiimide). 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide (EDC) can react with an antibody that functions as a capture molecule for the desired analyte. These coupling methods are known in the art and are within the ability of those skilled in the art with ordinary skill in the art. The surface of the nanowire can also be coated with a biocompatible binding layer, which can bind capture molecules to the surface of the nanowire. Examples of layers that can be used and have biocompatibility include collagen (type I, III or V), chitosan, heparin, as well as fibronectin, decorin, hyaluronic acid, chondroitin sulfate, heparan sulfate, and growth factor Still other components such as (TGFβ, bFGF) can be mentioned. Another example of a biocompatible binding layer is an aminosilane film, in which a thiol-modified deoxyribonucleic acid (DNA) oligomer that functions as a capture molecule, for example, a thiol-reactive component and an amino reaction. It can be immobilized via a heterobifunctional cross-linking molecule containing both sex components.

In another embodiment of the nanowire sensor, the nanowire sensor further comprises a cap layer over the insulating layer that closes the microfluidic channel.
In another embodiment of the nanowire sensor, the cap layer includes at least two openings, each opening being located at a distance away from each support.

In another embodiment of the nanowire sensor, the nanowire sensor further comprises a second insulating layer disposed between the support substrate and the semiconductor fin structure.
In yet another embodiment of the nanowire sensor, the nanowire sensor comprises a passivation layer over the first conductive layer and between the first conductive layer and the first insulating layer.

In another embodiment of the nanowire sensor, the nanowire sensor further comprises an electrode. The electrode is located under the nanowire and between the support substrate and the nanowire.
In another embodiment of the nanowire sensor, the nanowire sensor further comprises a third insulating layer disposed between the electrode and the nanowire.

The present invention further provides a nanowire sensor array comprising a plurality of nanowire sensors, wherein each nanowire sensor can be individually designated via a support.
In one embodiment of the nanowire sensor array, the array comprises a plurality of microfluidic channels.

In another embodiment of the nanowire sensor array, the array comprises a control unit that individually designates each nanowire sensor.
In yet another embodiment of the nanowire sensor array, in the array, one nanowire sensor is used as a reference and another nanowire sensor is used for measurement.

  The present invention further provides a detection method using a nanowire sensor array. The method uses one nanowire sensor as a reference and another nanowire sensor for measurement.

  The present invention further provides a method for detecting an analyte. The method includes measuring a first electrical signal of the nanowire sensor, contacting the nanowire sensor with a sample suspected of containing an analyte of interest, fixing the analyte to the nanowire, and measuring a second electrical signal of the nanowire. And detecting the presence or absence of the specimen by comparing the measured first electrical signal with the second electrical signal.

  In another embodiment of the method for detecting an analyte, the method further comprises providing a capture molecule that binds the analyte on the surface of the nanowire; and then contacting the sample suspected of containing the analyte of interest with the capture molecule. Allowing the formation of a complex between the analyte and the capture molecule.

In another embodiment of the method for detecting an analyte, the presence of the analyte is detected when the difference between the first electrical signal and the second electrical signal exceeds a threshold.
In another embodiment of the method for detecting an analyte, the analyte is a biopolymer, a living organism, or a small organic molecule.

1 shows a top view of a nanowire sensor according to a first embodiment of the invention. FIG. 2 shows cross-sectional views of a nanowire sensor in various forming steps according to a first embodiment of the present invention. FIG. 2B-1 and 2B-2 show cross-sectional views of the nanowire sensor in various formation steps according to the first embodiment of the present invention. 2 shows cross-sectional views of a nanowire sensor in various forming steps according to a first embodiment of the present invention. FIG. 2 shows cross-sectional views of a nanowire sensor in various forming steps according to a first embodiment of the present invention. FIG. 2 shows cross-sectional views of a nanowire sensor in various forming steps according to a first embodiment of the present invention. FIG. 2 shows cross-sectional views of a nanowire sensor in various forming steps according to a first embodiment of the present invention. FIG. 2 shows cross-sectional views of a nanowire sensor in various forming steps according to a first embodiment of the present invention. FIG. 2 shows cross-sectional views of a nanowire sensor in various forming steps according to a first embodiment of the present invention. FIG. 2 shows cross-sectional views of a nanowire sensor in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a flowchart of a method for forming a sensor comprising nanowires on a support substrate having a first semiconductor layer disposed on the support substrate, according to a first embodiment of the present invention. FIG. 6 shows a top view of a nanowire sensor having a through via on a cap layer according to a second embodiment of the present invention. FIG. 3 shows a cross-sectional view of a nanowire sensor according to a second embodiment of the present invention. FIG. 6 shows a top view of a nanowire sensor having bonding pad openings on a cap layer according to a third embodiment of the present invention. FIG. 4 shows a cross-sectional view of a nanowire sensor according to a third embodiment of the present invention. Fig. 4 shows nanowires that are structurally different. Fig. 4 shows nanowires that are structurally different. Fig. 4 shows nanowires that are structurally different. Fig. 4 shows nanowires that are structurally different. Fig. 4 shows nanowires that are structurally different. Fig. 4 shows nanowires that are structurally different. 2 shows different functional types of nanowires. 2 shows different functional types of nanowires. 2 shows different functional types of nanowires. 2 shows different functional types of nanowires. 1 schematically illustrates a nanowire sensor array. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. FIG. 2 shows a top view and a cross-sectional view of a nanowire sensor array in various forming steps according to a first embodiment of the present invention. 2 shows different prototypes of fluid channel formation. FIG. 4 shows a top view of a fluid channel covered with a cap layer. Fig. 6 illustrates different multiplexed nanowire sensor array schemes with a reference nanowire array and a fluid channel. Fig. 6 illustrates different multiplexed nanowire sensor array schemes with a reference nanowire array and a fluid channel. 4 shows a multiplexed nanowire array applying four different surface modification methods to different fluid channels, and a single reference nanowire array. 4 shows a multiplexed nanowire array that applies four different surface modification methods to a single fluid channel, and a multiplexed reference nanowire array. 4 shows another embodiment of a nanowire sensor array system. 4 shows another embodiment of a nanowire sensor array system. Fig. 2 shows a released single nanowire sensor formed in accordance with a first embodiment of the present invention. The high resolution transmission electron microscope (HRTEM) image of Si nanowire which shows a triangular cross section is shown. 3 shows an HRTEM image of a Si nanowire showing a circular cross section. 1 shows an overall view of a silicon nanowire array having 100 nanowires. Figure 2 shows a scanning electron microscope (SEM) photograph of a silicon nanowire array before forming a fluid channel. Fig. 3 shows different views of an array of Si nanowires arranged vertically and horizontally. Fig. 3 shows different views of an array of Si nanowires arranged vertically and horizontally. 3 shows the electrical properties of nanowires in a nanowire sensor array. Fig. 2 shows a pre-formed silicon nanowire array having different dimensions and integrated into a fluid channel. Fig. 2 shows a pre-formed silicon nanowire array having different dimensions and integrated into a fluid channel. Fig. 2 shows a pre-formed silicon nanowire array having different dimensions and integrated into a fluid channel. Fig. 2 shows a pre-formed silicon nanowire array having different dimensions and integrated into a fluid channel. ₂ shows n-type silicon nanowires embedded in SiO ₂ . Figure ₇ shows a graph of conductivity change versus pH measured for n-type silicon nanowires embedded in SiO2. Figure 7 shows a graph of conductivity change versus silicon nanowire width. An n-type silicon nanowire buried in SiO ₂ to be coated by another SiO ₂ layer. It measured about n-type silicon nanowire buried in SiO ₂ to be coated by another SiO ₂ layer, a graph of the change in the nanowire conductivity versus gate voltage (Vg) in the state of the presence or absence of buffer solutions of different pH Show. Figure 3 shows a graph of current (A)-voltage (V) measured for nanowire sensors before and after DNA attachment. The functionalization and DNA hybridization of probe DNA is shown schematically. The box plot of the electrical conductivity change when the DNA probe which hybridizes with ssDNA is fixed to p-type and n-type silicon nanowire arrays is shown. Shown is a box plot of conductivity change corresponding to different concentrations of probe DNA attached to an n-type silicon nanowire array; inset shows box plot of conductivity change when complementary DNA having a concentration of 1 pM hybridizes Indicates.

  The following figures illustrate various exemplary embodiments of the present invention. However, it should be noted that the present invention is not limited to the exemplary embodiments shown in the following figures and is further described in the following description.

  Exemplary embodiments of a sensor comprising nanowires on a support substrate with a semiconductor layer disposed on the support substrate are described in detail below with reference to the accompanying figures. Furthermore, the exemplary embodiments described below can be modified in various ways without changing the spirit of the present invention.

  FIG. 1 shows a top view of a nanowire sensor 102 comprising a single nanowire 104 made from a semiconductor material and integrated into a fluid channel 106 according to a first embodiment of the present invention. The nanowire sensor 102 can function as a block solution for a stand-alone device or for other lab-on-a-chip (LOC) applications. According to FIG. 1, the nanowire 104 is placed across the fluid channel 106 and has two corresponding ends. Each end of the nanowire 104 is connected to and supported by a corresponding support (not shown) made of a semiconductor material. Each end of the nanowire 104 is further connected to a corresponding electrical contact pad 110 via a support. The fluid channel 106 has an inflow port 112 and an outflow port 114, either or both of which can connect to and make connections from other blocks in the LOC.

  Next, cross sections along line XX shown in FIG. 1 of the sensor 102 in various forming steps are shown in FIGS. The features already described with respect to FIG. 1 will not be described again here. Although not described again, the same reference symbols refer to the same components.

  FIG. 2A shows the SOI structure 116 as the starting structure. The SOI structure 116 includes a semiconductor device layer 118 that is separated from the support substrate 122 by an insulating layer or a buried oxide (BOX) layer 120 in a vertical direction. The BOX layer 120 electrically insulates the element layer 118 from the support substrate 122. The SOI structure 116 can be formed by any standard method, such as a wafer bonding method or a separation by implantation of oxygen (SIMOX) method.

In the exemplary embodiment of the present invention of FIG. 2A, device layer 118 is typically Si (silicon), but can be formed of any suitable semiconductor material, and as a suitable semiconductor material, these are limited. Although not mentioned, mention may be made of polysilicon, gallium arsenide (GaAs), germanium or silicon germanium (SiGe). The element layer 118 can be initially doped with an n-type dopant to make the element layer an n-type layer, or doped with a p-type dopant to make the element layer a p-type layer. The film thickness of the element layer 118 is typically in the range of about 2 nanometers to about 1 micrometer. The support substrate 122 can be formed of any suitable semiconductor material, including but not limited to Si, sapphire, polycrystalline silicon (polysilicon), silicon oxide (SiO ₂ ) or Examples thereof include silicon nitride (Si ₃ N ₄ ). The BOX layer 120 is usually an insulating layer. The BOX layer 120 is typically SiO ₂ -based tetraethylorthosilicate (TEOS), silane (SiH ₄ ), or Si thermal oxide, glass, silicon nitride (with a film thickness in the range of about 2 nanometers to about several micrometers. Si ₃ N ₄ ) or silicon carbide can be mentioned, but is not limited to these materials.

  In an intermediate step after providing the SOI wafer 116 including the Si element layer 118 as a starting material, a photoresist layer (not shown) is applied or coated on the upper surface of the Si element layer 118. Next, the photoresist layer is patterned to form a FIN portion disposed between the two support portions by a standard photolithography method. Next, using the patterned photoresist layer as a mask, a portion of the Si element layer 118 that is not covered with the mask is etched away by an anisotropic etching process such as reactive ion etching (RIE).

  In FIG. 2B-1, a silicon FIN structure 128 composed of a silicon (Si) FIN portion 126 disposed between the corresponding Si support portions 108 and connected at each end to the corresponding Si support portion 108 is BOX. Formed on layer 120. The silicon FIN portion 126 functions as a bridge that connects the corresponding Si support portions 108. FIG. 2B-2 shows a top view of the FIN structure. The Si support portion 108 is generally a block having a relatively wide width as compared with the silicon FIN portion 126. FIG. 2B-2 shows a state in which the silicon FIN portion 126 is disposed at the center between the two Si support portions 108. As another configuration, the silicon FIN portion 126 may be disposed so as to be biased to either side of the two Si support portions 108. The resulting FIN structure 128 is similar to the FIN portion connecting the source and drain regions in the FINFET structure. This type of FINFET structure is described, for example, in US Pat. No. 6,764,884 and US Pat. No. 6,885,055. After forming the FINFET structure 128, the photoresist layer is removed or stripped by a photoresist stripper (PRS). Photoresist stripping or simply “resist stripping” is the removal of unwanted photoresist layers from a wafer. The purpose of photoresist stripping is to remove the photoresist material from the wafer as quickly as possible so that the chemical material used does not attack the surface material under the photoresist. In this regard, the flexibility of forming a FIN structure 128 including a silicon FIN portion 126 disposed between two Si supports 108 on the BOX layer 120 by using any other suitable technique or process. It can also improve sex.

Next, a self-limiting oxidation process is performed on the structure 128 including the silicon FIN portion 126 disposed between the two Si support portions 108. J. et al. Vac. Sci. Technol. As described by Jakub Kedzierski and Jeffer Bokor, published in B 15 (6), Nov / Dec 1997, self-limiting oxidation is not limited to these, but Si, silicon germanium, germanium, polycrystalline silicon, and A semiconductor material such as polycrystalline germanium is oxidized in a dry oxygen (O ₂ ) atmosphere at an approximate temperature range of about 800 ° C. to about 1200 ° C. and for a processing time of about 2 hours to about 10 hours to form SiO 2 _This is a process of forming a Si core surrounded by _two parts or a SiO ₂ film. During the self-limiting oxidation process, Si is oxidized to SiO ₂ . Since SiO ₂ occupies a larger volume than Si, as the oxidation proceeds, the newly formed inner oxide layer pushes the already formed oxide layer outward. Due to the high viscosity of SiO ₂ , the outer oxide film layer hardly undergoes plastic deformation in the radial direction, and as a result, a large normal stress is generated in the direction of returning to the Si—SiO ₂ interface. The normal stress at the Si interface acts to slow down the oxidation rate by making the transition from Si to SiO ₂ less energetically favorable. Eventually, at a given radius, oxidation will occur at a very slow rate, resulting in an oxidized structure comprised of one or more thin Si cores surrounded by a SiO ₂ film or SiO ₂ portion. can get. The number and size of the Si cores varies with the temperature and time of oxidation and can be controlled by setting the corresponding experimental conditions and the aspect ratio of the initial structure.

In FIG. 2C, the oxidized is constituted by a thin Si core 132 surrounded by a SiO ₂ part or SiO ₂ film 136 disposed between two thick Si cores 134 surrounded by another SiO ₂ part or SiO ₂ film 138. Structure 130 is formed after self-limiting oxidation treatment is applied to entire structure 128. With this process, a structure 128 including a silicon FIN portion 126 disposed between two Si supports 108 is disposed between two thick Si cores 134 surrounded by another SiO ₂ portion or SiO ₂ film 138. The structure is changed to the oxidized structure 130 constituted by the thin Si core 132 surrounded by the SiO ₂ portion or the SiO ₂ film 136. The Si core 132 surrounded by the SiO ₂ part or the SiO ₂ film 136 is formed as a result of oxidizing the silicon FIN part 126. _Two thick Si cores 134 surrounded by the SiO ₂ part or SiO ₂ film 138 are formed as a result of oxidizing the two Si supports 108.

However, the oxidation can also be limited to the silicon FIN portion 126 only (not shown in FIG. 2C). By oxidizing only the silicon FIN portion 126, the dimension of the thin Si core 132 surrounded by the SiO ₂ portion or the SiO ₂ film 136 is reduced. The thin Si core 132 is supported at the corresponding end by two non-oxidized Si supports 108. Any of these embodiments can be implemented depending on the requirements.

  In both embodiments described above where a self-limiting oxidation process is performed, the thin Si core 132 is on or above the box layer 120 and between the unoxidized Si support 108 or as a result of the Si support 108. It can be located at any height between the resulting Si cores 134. The thin Si core 132 ultimately constitutes the nanowire 104 in the present invention.

After the self-limiting oxidation process, a SiO ₂ layer 124 is deposited on the oxidized structure 130, as shown in FIG. 2D. This SiO ₂ layer 124 can be the same as the SiO ₂ part or SiO ₂ film 136 surrounding the thin Si core 132 and the SiO ₂ part or SiO ₂ film 138 surrounding the thick Si core 134. However, the SiO ₂ layer 124 is relatively thick compared to the corresponding SiO ₂ portion or SiO ₂ film 136, 138, and the two thick Si cores 134 are not affected by subsequent metal deposition or etching processes. Function to protect. SiO ₂ layer 124 and the respective SiO ₂ parts or SiO ₂ film 136, 138 may be those of SiO ₂ is fused in the case composed of the same material.

In the intermediate step, after the SiO ₂ layer 124 is deposited, a photoresist layer (not shown) is deposited on the SiO ₂ layer 124. Contact openings or contact recesses are formed in the photoresist layer by standard photolithographic methods to treat the SiO ₂ layer 124 covering the corresponding upper surface of the Si support 108, or SiO ₂ surrounding the two thick Si cores 134. Allows processing of the SiO ₂ layer 124 covering 138. A part of the SiO ₂ layer 124 and the SiO ₂ part or the SiO ₂ film 138 surrounding the two thick Si cores 134 are further etched to expose a part of the two thick Si cores 134.

  Next, in FIG. 2E, approximately 1000-15000 angstroms of conductive layer 140 is deposited so as to enter the contact openings and a portion of conductive layer 140 is contacted with two thick Si cores 134. In the exemplary embodiment, each portion of conductive layer 140 that contacts thick Si core 134 may be a 0.18 micron via or hole. The conductive layer 140 is typically a metal or metal alloy. Examples of metals include, but are not limited to, aluminum, various proportions of Si, aluminum alloyed with copper (Cu), tantalum, tantalum nitride, titanium, titanium nitride, or combinations of these metals. Can do. After the conductive layer 140 is deposited, standard photolithography and metal etching methods are performed so that the contact lines (not shown in FIG. 2E) further reach the electrical contact pads 110 (shown in FIG. 1) from the contact openings. Is defined using Next, the photoresist layer is removed by a photoresist stripping apparatus or stripped.

After the conductive layer 140 is deposited so as to enter the contact opening, the passivation layer 141 is deposited on the conductive layer 140 as shown in FIG. 2E. The passivation layer 141 can be formed of any suitable semiconductor material, and suitable semiconductor materials include Si, sapphire, polycrystalline silicon (polysilicon), silicon oxide (SiO ₂ ), or silicon nitride (Si ₃ N). ₄ ). The passivation layer protects the metal lines and the test solution from any reaction and helps to reduce non-specific binding of analytes or molecules in regions other than the thin Si core or nanowire.

Next, in FIG. 2F, an insulating layer 142 having a thickness in the range of about 1 micrometer to about several hundreds of micrometers is formed on the passivation layer 141 and the upper surface of the SiO ₂ portion 136 surrounding the thin SiO ₂ core 132. Is deposited on the SiO ₂ layer 124 overlying. Insulating layer 142 may be, for example, an oxide layer (such as SiO ₂ ), SU8, polydimethylsiloxane (PDMS), acetate, Riston, Kapton, a polymer such as polyimide and polyester, or other It can be a dielectric material. The thickness of the insulating layer 142 provides some depth for forming the channel after this step. After deposition, the insulating layer 142 can be further planarized using a polishing process, which can include chemical mechanical polishing (CMP), chemical polishing, mechanical polishing, or ion milling. it can. Since the polishing process provides a flat surface, a cap layer can be further deposited. However, for polymers such as SU8, planarization is not necessary.

In another intermediate step, a further photoresist layer (not shown) is deposited on the insulating layer 142. The photoresist layer is patterned by standard photolithography to form an opening over the area where the channel 106 is to be formed in the insulating layer 142. In FIG. 2G, a portion of the insulating layer 142 is etched away by an etching process such as dry etching to form a channel 106 using the photoresist layer as a mask to form a SiO ₂ surrounding the thin Si core 132. The upper surface of the part 136 can be processed, but the SiO ₂ part 136 remains at the position of the thin Si core 132. Dry etching is an etching process in which material is removed from the wafer without utilizing any liquid chemicals or etchants, and only volatile byproducts are produced in the process. Dry etching can be performed by any of the following processes: 1) a process utilizing a chemical reaction that removes the material using a chemical reaction gas or plasma; 2) the material is usually physically transferred by momentum transfer. Or 3) a combination of both physical removal and chemical reaction. In the exemplary embodiment, if the insulating layer 142 is a polymer such as SU8, the channel 106 is formed in a step after forming the opening by depositing or coating another photoresist layer. Although it is not necessary to form it, this is because SU8 is a type of photoresist. Ultraviolet (UV) light or an electron beam can be irradiated through the mask, and after development and baking, the channel 106 can be formed in the insulating layer 142.

After the dry etching step, the photoresist layer (if the photoresist layer has been deposited at a previous time) is then completely removed or stripped by a photoresist stripper. An etching process such as wet etching is used to release the thin Si core 132 from the surrounding SiO ₂ portion 136. Unlike dry etching, wet etching is the removal of material by immersing the wafer in a liquid bath containing a chemical etchant. The chemical etchant may be, for example, dilute hydrofluoric acid, buffered hydrofluoric acid such as Buffered Oxide Etch (BOE), (HF), and hydrofluoric acid (HF) containing hydrofluoric acid vapor. Any other suitable etchant that removes SiO ₂ can be used. However, it should be noted that the SiO ₂ portion 136 around the thin Si core 132 may not be completely removed by the etching process. The SiO ₂ part 136 can be thinned to several nanometers on the thin Si core 132, or the bottom surface of the thin Si core 132 is in contact with the SiO ₂ part 136 from the surface of the thin Si core 132, for example, from the top surface. It can be partially removed as is. This structure can act to impart physical strength to the thin Si core 132. After the etching step, from FIG. 2H, the resulting structure includes a thin Si core 132 (which constitutes the nanowire 104), and the thin Si core 132 is covered by the SiO ₂ portion 136 housed in the channel 106. It will be appreciated that it may or may not be coated.

  In FIG. 2I, after releasing the thin Si core 132 or nanowire 104, a cap layer 144 is further deposited on the top surface of the insulating layer 142. The cap layer 144 can be formed of any suitable material, which can include, but is not limited to, silicon, glass, silica, organic polymer, or PDMS. The cap layer 144 can include a fluid input port and an output port and can function to confine the channel 106 that houses the thin Si core 132 or nanowire 104. In another embodiment, the cap layer 144 has an opening or channel that complements the fluid channel 106 in the insulating layer 142 to provide a relatively large channel so that a relatively large amount of fluid is present. It can also be allowed to flow through the channel. This process completes an integrated sensor device that includes a thin Si core 132 or nanowire 104 and a fluid channel 106.

A flow chart of a method 300 for forming a sensor comprising nanowires on a support substrate with the semiconductor layer disposed on the support substrate shown in FIGS. The method 300 begins at step 302 with providing an SOI structure 116 as a starting material, the SOI structure 116 including a Si device layer 118 that is vertically oriented by a buried oxide (BOX) layer 120 from a support substrate 122. Separated. Next, in step 304, a photoresist layer is coated on the upper surface of the element layer 118. Next, the photoresist layer is patterned to form a FIN portion disposed between the two support portions by a standard photolithography method. Using the FIN patterned photoresist layer as a mask, the portion of the Si element layer 118 that is not covered by the mask is etched away to provide a silicon FIN 126 disposed between the two Si supports 108 on the BOX layer 120. A structure 128 constituted by is realized. In step 306, the structure 128 including the silicon FIN 126 between the two Si supports 220 is further subjected to a self-limiting oxidation process to form two thick Si cores 134 between the two cores. Oxidized structure 130 is provided that is included in the disposed state, where all cores are surrounded by SiO ₂ portions 136,138. Next, in step 308, an oxide layer 124 is deposited on the oxidized structure 130. Next, in step 310, a contact opening is formed, and a metal layer 140 is further deposited on the SiO ₂ layer 124 covering the corresponding upper surface of the SiO ₂ portion 138 surrounding the two thick Si cores 134, In some cases, a portion of the metal layer 140 contacts two thick Si cores 134. Yet another passivation layer 141 is deposited on the metal layer 140. Next, in step 312, an insulating layer 142 is deposited on the passivation layer 141 and on the SiO ₂ layer 124 covering the top surface of the SiO ₂ portion 136 surrounding the thin Si core 132. The insulating layer 142 is further planarized. However, if the insulating layer 142 includes a polymer such as SU8, planarization is not necessary. In step 314, a part of the insulating layer 142 is etched by dry etching to form the channel 106, thereby enabling processing on the upper surface of the SiO ₂ portion 136 surrounding the thin Si core 132, but the SiO ₂ portion 136. Remains at the position of the thin Si core 132. Next, in step 316, the SiO ₂ portion 136 surrounding the thin Si core 132 is etched by wet etching to release the nanowire 104 or sensor element. Finally, in step 318, the channel 106 is capped using a suitable cap substrate such as glass or PDMS.

  Various cap structures have been proposed to close the channel. 4A shows a top view of a sensor 102 using a cap structure according to a second embodiment of the present invention, and FIG. 4B shows a cross-section when the sensor 102 of FIG. 4A is cut along line XX. . The cap structure shown in FIGS. 4A and 4B according to the second embodiment of the present invention is different from the cap structure shown in FIG. 1 according to the first embodiment of the present invention. In the sensor 102 shown in FIG. 4A, a nanowire 104 is placed across the fluid channel 106 and has two ends. Each end of the nanowire 104 is connected to the through-wafer via 146 via the conductive layer 140. The fluid channel 106 has an inflow port 112 and an outflow port 114, either or both of these ports making connections to and from other blocks in the LOC. Can do. In FIG. 4B, the cap layer 144 can be a thin wafer with large sized through-wafer vias 146. The through-wafer via 146 can be formed by standard photolithography and etching methods. The through wafer vias 146 are then filled with the conductive layer 140 to form electrical connections from each via 146 to the corresponding thick Si core 134. Each end of the nanowire 104 is supported by a corresponding thick Si core 134. In FIGS. 4A and 4B, each through-wafer via 146 in the cap layer 144 is located at a predetermined distance from each corresponding thick Si core 134 and thus from the nanowire 104. One advantage of this arrangement is that it can eliminate misalignment that can occur during formation of the through-wafer via 146 prior to depositing the conductive layer 140. If these vias 146 are located very close to the nanowires 104, the conductive layer 140 will be deposited on the nanowires 104 even with a slight misalignment.

  FIG. 5A shows a top view of a sensor 102 using another cap structure according to a third embodiment of the present invention, and FIG. 5B shows a cross-section when the nanowire sensor 102 of FIG. 5A is cut along line XX. Show. The cap structure shown in FIGS. 5A and 5B according to the third embodiment of the present invention is the same as the cap structure shown in FIG. 1 according to the first embodiment of the present invention and FIGS. 4A and 4B according to the second embodiment of the present invention. It is different from the cap structure shown in 4B. In the sensor 102 shown in FIG. 5A, a nanowire 104 is placed across the fluid channel 106 and has two corresponding ends. Each end of the nanowire 104 is connected to the bonding pad opening 148 through the conductive layer 140. The fluid channel 106 has an inflow port 112 and an outflow port 114, either or both of these ports making connections to and from other blocks in the LOC. Can do. In FIG. 5B, the cap layer 144 is constituted by a corresponding bonding pad opening 148 for making a connection with the conductive layer 140 connecting the corresponding thick Si core 134. Each end of the nanowire 104 is supported by a corresponding thick Si core 134. The third embodiment of FIGS. 5A and 5B differs from the second embodiment of FIGS. 4A and 4B in that a bonding pad opening is formed after a portion of the cap layer 144 is etched away to form a bonding pad opening 148. The difference is that the conductive layer 140 is not filled in the portion. However, similar to FIGS. 4A and 4B, each bonding pad opening of these bonding pad openings 148 is located a predetermined distance away from each corresponding thick Si core 134 and thus nanowire 104. This arrangement prevents the problem of misalignment while the bonding pad opening 148 is being formed. In either the embodiment of FIGS. 4A and 4B and the embodiment of FIGS. 5A and 5B, the signal applies a potential to the respective conductive layer 140 of the through-wafer via 146 of FIG. 4B, or the respective of FIG. 5B. It can be measured by applying a potential to the bonding pad opening 148 and measuring the current flowing between these conductive layers or openings.

The nanowire sensor according to the present invention can comprise nanowires with different structural arrangements. Some of these arrangements are shown in FIGS. 6A-6F. FIG. 6A shows a nanowire sensor 102 composed of a single nanowire 104 disposed between two supports 108, and FIG. 6B shows two single nanowires 104 between two supports 108. The nanowire sensor 150 comprised by this arrangement | positioning is shown. As shown in FIG. 6C, a nanowire sensor 152 configured by arranging a plurality of (at least three nanowires) single nanowires 104 disposed between two support portions 108 as required is realized. You can also FIG. 6D shows a nanowire array 154 constructed by placing two single nanowire sensors 102 in parallel. Each single nanowire sensor 102 comprises a single nanowire 104 disposed between two supports 108, similar to the nanowire sensor shown in FIG. 6A. More than two single nanowire sensors 102 can be placed in parallel or along the direction of fluid flow depending on requirements. Further, the “double (having two nanowires)” nanowire sensor 150 shown in FIG. 6B, the “multi (having multiple nanowires)” nanowire sensor 152 shown in FIG. 6C, or a combination of both of these nanowire sensors are parallel. It can also be arranged. FIG. 6E shows a nanowire sensor 156 composed of a long single nanowire 104 that passes through several Si blocks or SiO ₂ blocks 158 disposed between two supports 108. However, any suitable number of nanowires can be utilized depending on the requirements. Furthermore, the nanowires can be arranged in any suitable arrangement or in any desired pattern. FIG. 6F shows a nanowire sensor array 160 comprising a plurality of single nanowires 104 that pass through several Si blocks or SiO ₂ blocks 158 disposed between two supports 108. If necessary, contact the sample by such an arrangement, for example by using a zigzag arrangement or any other arrangement, taking into account that the size must be kept small and the concentration of the target molecule is low Since the surface area to be increased can be increased, the detection function by the nanowire sensor can be enhanced. Basically, there are a large number of nanowire structure arrangements to meet different requirements.

  Nanowire sensors according to the present invention can also comprise nanowires with different functions, some of which have different functions are shown in FIGS. 7A-7D. In the embodiment shown in FIG. 7A, highly precise doping can be performed on the nanowire to form a sensor comprising an n-type or p-type nanowire 162. The n-type or p-type nanowire 162 can be disposed between the two supports 108. P-type nanowires can be formed using p-type dopants including, but not limited to, boron, aluminum, gallium, and indium, and n-type including, but not limited to, phosphorus, arsenic, and antimony The dopant can be used as a dopant for forming the n-type nanowire. The doping on the nanowire can be performed after the self-limiting oxidation step of FIG. 2C, or the doping can be performed at any step prior to the formation of the nanowire sensor. A preferred ion implantation step is performed before the self-limiting oxidation step.

  In another embodiment shown in FIG. 7B, a sensor comprising a nanowire having a P / N diode junction 164 can be realized. A nanowire having a P / N diode junction 164 can be placed between the two supports 108. A nanowire having a P / N diode junction 164 is realized by partially doping one portion of the nanowire with an n-type dopant and partially doping another portion of the nanowire with a p-type dopant. Multiple P / N diode junctions can also be realized on the same nanowire. The step of doping the nanowire with a composite dopant comprising a p-type dopant and an n-type dopant to form a nanowire having a P / N diode junction 164 can also be performed after the self-limiting oxidation step of FIG. It can also be performed in any step prior to formation.

In yet another embodiment shown in FIG. 7C, a sensor comprising a silicided nanowire 166 having one or more nanogap 168 can be realized. Silicided nanowire 166 can be disposed between two supports 108. In this embodiment, the portion or portions of the Si nanowire that define the nanogap 168 are covered by a dielectric layer, typically a SiO ₂ layer, or any other suitable dielectric material layer. The remaining portion of the Si nanowire is covered by a conductive layer, which can include, but is not limited to, metals such as tungsten and nickel, and metal alloys. Next, the Si nanowire is heat-treated to change the portion of Si that contacts the metal layer into metal silicide. The unreacted metal is then removed in an acidic solution such as sulfuric acid. The dielectric material layer is also removed.

  In yet another embodiment shown in FIG. 7D, Si nanowires 170 having one or more nanogap 168 can be realized. The Si nanowire 170 can be disposed between the two support portions 108. Part or portions of the Si nanowire 170 can be selectively etched using a selection mask to form a nanogap or nanogap group 168. Etching is performed in any one of the appropriate process steps, for example after the time when the fin 126 of FIG. 2B-1 is formed, after the self-limiting oxidation step of FIG. 2C, or when the nanowire of FIG. Can be done after being released. Other etching methods such as dry etching or wet etching, lithography or focused ion beam etching can also be used.

  A plurality of nanowires may be formed in an array to increase the probability of attachment of target biomolecules or molecular species. This configuration is also very useful for detection at low concentrations. Second, each nanowire in the array can be individually measured for the conductivity of that wire. This essentially increases the sensitivity of the nanowire array, but this means that most of the current flows through one nanowire and hardly flows into another nanowire, which reduces the change in conductivity. Because there is no such thing. Third, each nanowire can be integrated with a microfluidic channel to deliver a target biomolecule to the detection nanowire. Fourth, multiplex analysis can be performed by functionalizing the group of nanowires in the array to induce specific binding or causes. Fifth, using a suitable fluid design, a different series of nanowire arrays can be used in parallel for various analyzes of biomolecules. Finally, additional back gate electrodes can be incorporated for each array, for individual nanowires, or for nanowire groups to selectively modify surface binding properties. This configuration can be an attractive means, and by this means molecules can be selectively bound, so this means can be a way to identify specific molecules. Thus, nanowire sensor arrays can be a useful tool for analyzing a range of new phenomena.

  FIG. 8 schematically illustrates a multiple nanowire sensor array 192, where a plurality of nanowire sensor arrays 182 are connected to a parallel fluid channel 190 having a common analyte input 194 and output 196. In the enlarged view, each nanowire sensor array 182 can have two nanowire arrays, one nanowire array being a nanowire array for analyzing an analyte or biomolecule, referred to as a “sensor array” 184, and the other Is a nanowire array for a reference buffer solution and is referred to as a “reference array” 186. By integrating each nanowire sensor array 182 individually with a fluid channel 190, an input port 194, and an output port 196, fluid can flow. Each nanowire sensor in the array can be individually measured for the change in conductivity of the sensor, and all of the nanowire groups can be electrically interfaced with the circuit on-chip or off-chip. This change in conductivity can be measured by the control electronics block 188 shown in FIG. Once the sensor groups of each array 182 are identifiably modified with an appropriate chemical reagent, these sensors can detect various biomolecule groups or marker groups simultaneously. Each nanowire sensor array 182 can operate based on a change in conductivity, which is caused by stress due to charge or mass when a biomolecule is immobilized on the nanowire sensor element by appropriate surface modification. obtain. Furthermore, it is not necessary to provide two nanowire arrays corresponding to all application modes. Depending on the application, one or more than two nanowire arrays are suitable. Also, there is no need to provide a separate “reference array”. The array itself can serve as a pre-measurement reference. In this case, both arrays can operate as separate arrays.

  9A-9N show top and cross-sectional views, respectively, of a nanowire sensor array in various formation steps according to one embodiment of the present invention. These forming steps are the same as the forming steps shown in FIGS. 2A to 2I except that three steps shown in FIGS. 9C, 9D, and 9E are added. The back gate electrode is formed before forming the nanowire.

  FIG. 9A shows the support substrate 122 as the starting material. FIG. 9B shows how an insulating or buried oxide (BOX) layer 120 is deposited on the support substrate 122. In order to form the back gate electrode, the second semiconductor element layer 119 is deposited on the insulating layer or the BOX layer 120 as shown in FIG. 9C. The second semiconductor element layer 119 can be formed of the same material as the first semiconductor element layer 118 (already shown in FIG. 2A) and is typically Si, but should be formed of any suitable semiconductor material. Suitable semiconductor materials can include, but are not limited to, polysilicon, gallium arsenide (GaAs), germanium, or silicon germanium (SiGe).

  After the second semiconductor element layer 119 is deposited, a photoresist layer (not shown) is applied or coated on the upper surface of the Si element layer 119. Next, the photoresist layer is patterned to form at least two electrodes by standard photolithography. Next, using the patterned photoresist layer as a mask, the portion of the second semiconductor element layer 119 that is not covered by the mask is etched away by an anisotropic etching process such as reactive ion etching (RIE). To do. The resulting at least two electrodes 121 are formed on the BOX layer 120 as shown in FIG. 9D.

  Next, a second insulating layer 123 is deposited on each electrode 121 and on the BOX layer 120 as shown in FIG. 9E. Next, another semiconductor layer or first semiconductor element layer 118 (as shown in FIG. 2A) is deposited on the second insulating layer 123 as shown in FIG. 9F. A photoresist layer (not shown) is applied or coated on the upper surface of the first semiconductor element layer 118. Next, the photoresist layer is patterned to form a FIN portion disposed between the two support portions by a standard photolithography method.

  Next, using the patterned photoresist layer as a mask, a portion of the first semiconductor element layer 118 that is not covered by the mask is etched away by an anisotropic etching process such as reactive ion etching (RIE). To do. A silicon FIN structure 126 is provided between the corresponding Si support portions 108 and connected at each end to the corresponding Si support portion 108, and the resulting silicon FIN structure 128 includes the second insulating layer 123. It is formed as shown in FIG. 9G.

Next, the structure 128 including the silicon FIN portion 126 disposed between the two Si support portions 108 is subjected to self-limiting oxidation treatment. By this process, the structure 128 including the silicon FIN portion 126 disposed between the two Si support portions 108 is converted into another SiO ₂ portion or SiO ₂ film (on the dimension basis) on the second insulating layer 123 shown in FIG. 9H. (Not shown in FIG. 9H for this reason) and surrounded by a SiO ₂ portion or SiO ₂ film (not shown in FIG. 9H for dimensional reasons) disposed between two thick Si cores 134. Change to an oxidized structure 130 composed of a thin Si core 132. The Si core 132 surrounded by the SiO ₂ part or the SiO ₂ film is formed as a result of oxidizing the silicon FIN part 126. _Two thick Si cores 134 surrounded by SiO ₂ parts or SiO ₂ films are formed as a result of oxidizing the two Si supports 108. The thin Si core 132 finally constitutes the nanowire in the present invention.

After the self-limiting oxidation process, a SiO ₂ layer 124 is deposited on the oxidized structure 130 as shown in FIG. 9I. The SiO ₂ layer 124 may be a thin Si core 132 surrounds SiO ₂ parts or SiO ₂ film, and surrounding the two thicker Si core 134 SiO ₂ parts or the same and the SiO ₂ film. However, SiO ₂ layer 124 is relatively thick compared to the respective SiO ₂ parts or SiO ₂ film, and the two thicker Si core 134 functions to protect the not affected by subsequent deposition. The SiO ₂ layer 124 and the respective SiO ₂ part or SiO ₂ film can be fused if these SiO ₂ are composed of the same material.

In the intermediate step, after the SiO ₂ layer 124 is deposited, a photoresist layer (not shown) is deposited on the SiO ₂ layer 124. Contact openings or contact recess by standard photolithography to form a photoresist layer, to enable processing on SiO ₂ layer 124 on the SiO ₂ parts surrounding the two thicker Si core 134. A portion of the SiO ₂ layer 124 and the SiO ₂ portion or SiO ₂ film surrounding the two thick Si cores 134 are further etched to expose a portion of the two thick Si cores 134. Next, a conductive layer 140 is deposited so as to enter the contact opening, and a portion of the conductive layer 140 contacts the two thick Si cores 134 as shown in FIG. 9J. Next, the photoresist layer is removed by a photoresist stripping apparatus or stripped.

After the conductive layer 140 is deposited so as to enter the contact opening, a passivation layer 141 is deposited on the conductive layer 140 as shown in FIG. 9K.
Next, as shown in FIG. 9L, an insulating layer 142 is deposited on the passivation layer 141 and on the SiO ₂ layer 124 covering the upper surface of the SiO ₂ portion surrounding the thin Si core 132. After being deposited, the insulating layer 142 can be further planarized using one of the polishing processes already described. The polishing process provides a smooth surface for further deposition of the cap layer. However, if the insulating layer is a polymer such as SU8, planarization is not necessary.

In another intermediate step, another photoresist layer (not shown) is deposited on the insulating layer 142. By patterning the photoresist layer by standard photolithography techniques, an opening is formed over the region where the channel 106 is to be formed in the insulating layer 142, as shown in FIG. 9M. Using the photoresist layer as a mask, a part of the insulating layer 142 is etched away by an etching process such as dry etching to form the channel 106, and the upper surface of the SiO ₂ portion surrounding the thin Si core 132 is processed. Although possible, the SiO ₂ part remains at the position of the thin Si core 132.

After the dry etching process, the photoresist layer is then removed or stripped by a stripper. An etching process is used to release the thin Si core 132 from the surrounding SiO ₂ part. In an exemplary embodiment, if the insulating layer 142 is a polymer such as SU8, for example, SU8 is also a type of photoresist, so another layer of photoresist is deposited or coated to form the channel 106. It is not necessary to form an opening for forming at a later time.

  After releasing the thin Si core 132 or nanowire, a cap layer 144 is further deposited on top of the insulating layer 142, as shown in FIG. 9N. The cap layer 144 can include a fluid input port and a fluid output port and can function to contain a channel 106 that houses a thin Si core 132 or nanowire.

  In summary, these forming steps are the same as the forming steps shown in FIGS. 2A to 2I except that three steps shown in FIGS. 9C, 9D, and 9E are added. In this step, the back gate electrode is formed before forming the nanowire. The purpose of forming a sensor array having a back gate structure is that the conductivity of each nanowire array can be varied individually using a back gate voltage. This structure can be an attractive option that can modify the surface binding or catalytic properties of the nanowires by an external electric field.

  FIG. 10 shows different prototypes of fluid channel formation. Diagram (a) of prototype 1 shows an input fluid channel that is split into two channels. Each channel of these two channels is further subdivided into another two channels. All of these channels are subsequently fused. Figures (b) and (c) of Prototype 1 show progressively enlarged views of a portion of the fluid channel of Prototype 1 (a). In figure (c) of prototype 1, silicon nanowires are accommodated in the channel. However, a plurality of nanowires can also be arranged in different parts of each of these detection channels according to requirements. Diagram (a) of prototype 2 shows four separate fluid channels that merge into one common fluid channel. Figure 2 (b) of prototype 2 shows how a plurality of nanowires can be placed in each fluid channel, but is not limited to this configuration.

  FIG. 11 shows a top view of the fluid channel 190 covered with the cap layer 144. The cap layer 144 can be a glass layer and the fluid channel 190 can be covered with the cap layer 144 using, for example, a low temperature bonding process of about 50 ° C. From FIG. 11, it can be seen that no leakage occurs and that the capping technique can be used and applied to the nanowire array.

  Figures 12A and 12B show different multi-fluid channel configurations in a nanowire array structure. FIG. 12A shows two different fluid channel configurations, one fluid channel configuration associated with sensor array 184 and the other fluid channel configuration associated with reference array 186. In the configuration associated with sensor array 184, a single fluid enters fluid channel 190 through fluid inlet 194 and exits through fluid outlet 196 having four individual fluid channels 190. To do. A single fluid channel 190 is divided into two fluid channels 190, and each fluid channel of these two fluid channels 190 is further subdivided into two further fluid channels 190 to provide four individual fluid channels. A channel 190 is formed, but is not limited to this configuration. The same fluid flows through all of these fluid channels 190, and the nanowire 104 is housed within each of the four fluid channels 190 for use in different analytical or detection purposes. The nanowires 104 in each fluid channel 190 constitute a sensor array 184. In the configuration associated with the reference array 186, fluid flows through the fluid inlet 194 into a single fluid channel 190 and is not further divided into other fluid channels 190. The nanowires 104 are again received in this single fluid channel 190 and the nanowires 104 in the single fluid channel 190 constitute the reference array 186. The results can be detected by sensor array 184 and reference array 186, respectively, and the corresponding signals can be read by control electronics block 188.

  FIG. 12B also shows two different fluid channel configurations. In both of these configurations, a single fluid enters the single fluid channel 190 through the fluid inlet 194 and exits through the fluid outlet 196 having four individual fluid channels 190. A single fluid channel 190 is divided into two fluid channels 190, and each fluid channel of these two fluid channels 190 is further subdivided into two other further fluid channels 190 to provide four individual channels. A fluid channel 190 is formed, but is not limited to this configuration. The same fluid flows through all of these fluid channels 190. The nanowires 104 are housed in each of the four channels 190 to perform different analysis or detection, respectively, and constitute a sensor array 184 and a reference array 186, respectively. Different analyzes can be performed depending on requirements using different multi-fluidic channel configurations in the nanowire array structure.

  The nanowire sensor array of the present invention can be utilized for numerous applications, such as sensor applications, or for drug discovery applications. For sensor applications, the nanowire sensor array can include a composite array of sensor array 184 and reference array 186, as shown in FIGS. 13A and 13B. In FIG. 13A, a series of different surface modification schemes can be applied to the series of nanowires 104, and these nanowires 104 are each housed in a plurality of fluid channels 190 that make up the sensor array 184. be able to. Another series of nanowires 104 can be accommodated in a single fluid channel 190 that constitutes the reference array 186 and can serve as a control. Both the sensor array 184 and the reference array 186 can have fluid flow by having corresponding inlets 194 and outlets 196. The inlet 194 and outlet 196 can be common to both the sensor array 184 and the reference array 186 or can be provided separately. The results can be detected by sensor array 184 and reference array 186, respectively, and the corresponding signals can be read by control electronics block 188. The surface modification can be an application specific type of modification and can be defined by the user. For example, a first array may be modified to detect / rabine anti-rabbit IgG antibodies on the array, and a second array may be modified to detect anti-murine IgG antibodies on the array / to the array. When bound, each array will capture only the corresponding anti-rabbit IgG antibody and anti-murine IgG antibody.

  In FIG. 13B, a series of nanowires can be applied to a plurality of different surface modification methods and can be accommodated in a single fluid channel 190 that comprises a sensor array 184. Another series of nanowires 104 can be housed in another single fluid channel 190 that constitutes the reference array 186 and can serve as a control. One reference array can be provided to correspond to each sensor array using different modification methods. In both FIGS. 13A and 13B, each nanowire may be accommodated in multiple channels, with each channel in the reference array 186 corresponding to each channel in the sensor array 184.

  For drug discovery applications, either of the two embodiments shown in FIGS. 14A and 14B can be utilized. In FIG. 14A, the nanowire sensor array can include a composite array of sensor array 184 and reference array 186. The sensor array 184 may be provided in a plurality of fluid channels 190 having corresponding inlets 194 and outlets 196, and the reference array 186 is a single fluid channel 190 having corresponding inlets 194 and outlets 196. Can be provided. Different compounds 198, or the same compound, can be injected into different respective fluid channels 190 of sensor array 184 at different doses or concentrations. The injected compound 198 will react with the target lesion. The results can each be detected by the downstream sensor array 184 and the reference array 186 and the corresponding signals can be read by the control electronics block 188. The inlet 194 and outlet 196 can be provided separately in both the sensor array 184 and the reference array 186 as shown in FIG. 14B, but the inlet 194 and outlet 196 are based on the requirements of the sensor array 184. And the reference array 186 may be provided in common.

  In FIG. 14B, the nanowire sensor array can include a composite array of sensor array 184 and reference array 186. The sensor array 184 may be provided in a plurality of fluid channels 190 having corresponding inlets 194 and outlets 196, and the reference array 186 is a single fluid channel 190 having corresponding inlets 194 and outlets 196. Can be provided. Different compounds 198 are immobilized on the surface of different channels 190 located upstream of the sensor array 184. The target lesion will react with these immobilized compounds 198 as fluid flows. The result will be detected by the downstream sensor array 184 and the reference array 186, respectively, and the corresponding signal can be read by the control electronics block 188. The inlet 194 and outlet 196 can be provided separately in both the sensor array 184 and the reference array 186, as shown in FIG. 14B, but the inlet 194 and outlet 196 are based on sensor requirements. It can also be provided in common for both the array 184 and the reference array 186.

Experimental Example A method for forming a sensor including nanowires on a support substrate and having a semiconductor layer disposed on the support substrate according to an embodiment of the present invention is described below. Based on. However, these experimental examples should not be taken as limiting the scope of the present invention.

  Experimental Example 1: When forming a Si nanowire, an SOI wafer having a diameter of 200 mm made of a Si element layer having a thickness of 200 nm and a BOX having a thickness of 150 nm on a supporting substrate was used. A trench was formed in the Si element layer by lithography and etching until reaching the BOX, thereby obtaining a silicon FIN having a width of 80 nm. Next, the wafer was oxidized in a dry oxygen atmosphere at 900 ° C. for 6 hours to form nanowires 104 shown in FIG. A single nanowire is one of the nanowire structure arrangements described in FIG. 6A. By doping with an n-type dopant, a p-type dopant, or a composite dopant of an n-type dopant and a p-type dopant, different functional group type nanowires can be realized as described in FIGS. 7A and 7B.

Experimental Example 2: High resolution transmission electron microscope (HRTEM) images of Si nanowires are shown in FIGS. 16A and 16B. FIG. 16A shows a nanowire 172 having a triangular cross section with a base 200 of about 10 nanometers and a height 202 of about 12.3 nanometers. The reason for the triangle is that different oxidation fronts travel along different crystal orientations. By using the viscoelastic properties of SiO _2, and Si atoms move in Si-SiO ₂ interface, caused by applying a circular deformation, the nitrogen _{(N 2)} annealing for one hour at about 1200 ° C. to the wafer It can also be made. A nanowire 174 having a circular cross section with a diameter of about 7.7 nanometers is shown in FIG. 16B. Therefore, the cross section of the nanowire can be triangular or circular, and the shape depends on the process conditions.

  A nanowire sensor array including a plurality of nanowire sensors having a configuration in which each nanowire sensor can be individually designated via a support according to an embodiment of the present invention is also described below based on the following experimental example. However, these experimental examples should not be taken as limiting the scope of the present invention.

FIG. 17 shows an overall view of a silicon nanowire array having 100 nanowires, each nanowire having a length of about 200 micrometers.
FIG. 18 shows a scanning electron microscope (SEM) photograph of the silicon nanowire array before forming the fluid channel. The inset shows an enlarged portion of the nanowire array.

  The array of Si nanowires 176 can be arranged vertically, horizontally (parallel and perpendicular to each other), or a combination of vertical and horizontal, as shown in FIGS. 19A and 19B. 19A and 19B show views of the array of Si nanowires 176 from different perspectives.

  FIG. 20 shows the electrical properties of the nanowires of the nanowire sensor array. The current (I) of the silicon nanowire is measured in amps (A), the voltage (V) is measured in volts (V), and the conductivity is measured and expressed in nanosiemens (nS). A conductivity vs. voltage plot is shown at 212 and a current vs. voltage plot is shown at 214. To measure the current-voltage characteristics of the nanowire, a variable potential (−0.5 V to +0.5 V) is applied across the nanowire and the corresponding current is measured. This current vs. voltage plot is referred to as the IV curve 214. Conductivity is calculated as the ratio of current to voltage. When measuring current, any standard ammeter can be used while the voltage is applied by a voltage generator. Conductivity versus voltage plot 212 shows that the conductivity of the sensor is very stable at about 100 nS. Current vs. voltage plot 214 shows that current varies linearly with potential.

  FIGS. 21A-21D show how different shaped silicon nanowire arrays that have been formed are integrated into a fluid channel. The two fluid channels are parallel to each other, and the silicon nanowire array is housed in each fluid channel. Silicon nanowire arrays have dimensions in the range of about 100 μm to about 1000 μm. FIG. 21A shows how a silicon nanowire array having a dimension of about 100 μm is received in a fluid channel. FIG. 21B shows how a silicon nanowire array having a dimension of about 200 μm is received in a fluid channel. FIG. 21C shows how a silicon nanowire array having a dimension of about 500 μm is received in a fluid channel. FIG. 21D shows how a silicon nanowire array having a dimension of about 1000 μm is received in a fluid channel. The nanowire array can be any other suitable dimension.

Since pH, ie, hydrogen ion index, is an indicator of the activity of hydrogen ions (H ⁺ ) in solution, it is the acidity of the ions. In aqueous systems, the activity of hydrogen ions is determined by the dissociation constant of water (K _W = 1.011 × 10 ⁻¹⁴ M ^{2 at} 25 ° C.) and interactions with other ions in solution. Due to this dissociation constant, the neutral solution (hydrogen ion activity equals hydroxide ion activity) has a pH of about 7. An aqueous solution having a pH value of less than 7 is considered acidic, and an aqueous solution having a pH value greater than 7 is considered basic. The pH detection can be performed using silicon nanowires. FIG. 22A shows an n-type silicon nanowire embedded in SiO ₂ . In FIG. 22A, the n-type silicon nanowire is a nanowire doped with an n-type dopant. FIG. 22B shows a graph of conductivity change vs. pH measured using n-type silicon nanowires embedded in SiO ₂ . The change in conductivity is measured in percent (%). The silanation process increases the adhesion of H ⁺ in solution to the n-type silicon nanowires. This increases the positive gate voltage and causes the deposition of H ⁺ on the n-type silicon nanowire, thus increasing the conductivity. The plot after the surface modification with silane is shown at 202 and the plot before the surface modification with silane is shown at 204. Thus, these experiments show that nanowire sensors can be used for fluid analysis without, for example, immobilizing capture molecules on the nanowire.

  FIG. 23 shows a graph of conductivity versus width for silicon nanowires when the nanowire length is fixed at 100 μm and the pH is about 1.95. The width of the silicon nanowire is measured in nanometers (nm) and the change in conductivity is measured in percent (%). FIG. 23 shows that the sensitivity increases because the conductivity change increases as the nanowire width decreases. This is because the electrostatic controllability to the gate is increased. Therefore, sensitivity can be further enhanced by narrowing the nanowire width and reducing the gate oxide film thickness.

An analysis of the backgate effect on the nanowire response is also performed. FIG. 24A shows an n-type silicon nanowire embedded in SiO ₂ covered by another SiO ₂ layer, and FIG. 24B shows an n-type silicon nanowire embedded in SiO ₂ covered by another SiO ₂ layer. 3 shows a graph of conductivity versus gate voltage (Vg) of n-type silicon nanowires when measured. The gate voltage is measured in volts and the conductivity is measured and displayed in nanosiemens (nS). In FIG. 24B, n-type silicon nanowires can be immersed in a solution of about pH 4, or about pH 10, or not at all. A plot when the n-type silicon nanowire is not immersed in any solution is shown at 206, a plot when the n-type silicon nanowire is immersed in a solution of about pH 4 is shown at 208, and the n-type silicon nanowire is about A plot when immersed in a pH 10 solution is indicated by reference numeral 210. As the pH of the solution increases, the conductivity at a given voltage decreases. Since this phenomenon appears due to the influence on the ion solution by applying a bias, it can be used to increase sensitivity.

  The nanowire sensor of the present invention is also suitable for biological applications, because the sensor operates based on a change in conductivity caused by stress due to charge or mass when the biopolymer is fixed to the fin portion. It is. The biopolymer can be bound directly to the FIN moiety or via a capture molecule. In order to facilitate the binding of biopolymers to the FIN part, at least the surface of the FIN part should be adapted as previously described to further facilitate the binding of biopolymers such as DNA. Can do. The current-voltage (IV) electrical characteristics of each exemplary nanowire sensor before and after DNA attachment are shown in FIG. The plot after DNA attachment is shown at 178 and the plot before DNA attachment is shown at 180. After DNA attachment, the current at the same predetermined voltage becomes larger than before DNA attachment.

The DNA probe is immobilized as shown in FIG. 26A. In the immobilization process, SiO ₂ is formed on the silicon nanowires, followed by silanization, and the capture molecules are coupled via linkage using NHS-biotin and streptavidin, as described in detail below. Fixed. The capture molecule has the sequence TTA ACT TTA CTC CCT TCC (SEQ ID NO: 1) and It was a single stranded 18 bp oligonucleotide designated Ec18c available from E. coli K12. E. nucleotide having the nucleotide sequence GGA AGG GAG TAA AGT TAA TAC CTT TGC TCA TTG ACG (SEQ ID NO: 2) and denoted Ec36T. An oligonucleotide from E. coli K12 was used as an exemplary target ssDNA sequence.

  FIG. 26A shows an exemplary binding experiment setup performed using the sensor of the present invention. First, the reactive hydroxyl group of silicon dioxide formed on the surface of the nanowire was reacted with an appropriate aminosilane to form a silane layer having free amino end groups, and then a desired capture molecule was immobilized. The biotin-N-succinimidyl ester was then reacted via conventional NHS binding to the silane layer. Utilizing the specific binding of streptavidin (or avidin) to biotin, an immobilizing agent is supplied by adding streptavidin to specifically immobilize each capture molecule, thereby providing background And the sensitivity of the sensor was further increased. Streptavidin is very suitable for this purpose (however, the present invention is in no way limited to the use of such immobilizing agents), which means that streptavidin is located on the opposite surface of the streptavidin molecule with a biotin binding site. (Streptavidin has four identical subunits, meaning that each of these subunits has one biotin binding site). Thus, the other two biotin binding sites can be utilized to bind biotinylated capture molecules while non-covalently bound to the silane layer via one or two biotin binding sites.

  In the experimental example described here, an oligonucleotide having the sequence of SEQ ID NO: 1 was used as the capture molecule. However, it is clear that any other capture molecule whose presence has an affinity for the desired ligand to be studied can be used in combination with the sensor of the present invention. For example, such capture molecules bind to antibodies that are biotinylated and bind to small organic molecules such as environmental toxins such as DDT, or viruses such as human immunodeficiency (HIV) virus or hepatitis C virus. It can be an antibody (or more precisely an antibody that binds to the surface structure of the virus). Thus, using such capture molecules, the sensor of the present invention can be used for environmental or diagnostic purposes.

  Furthermore, the sensor of the present invention can also be used for drug screening. In such embodiments, the capture molecule can be a protein that is a drug target, such as, for example, vascular endothelial growth factor (VEGF). Since this drug target can be biotinylated, it can be immobilized on the nanowire surface. Next, the nanowire surface is brought into contact with a solution containing phagemids, and the phagemid deposits antibody fragments suspected of having binding affinity for VEGF on the phagemid surface. These phagemids can be prepared, for example, according to any conventional “phage display” method, see Curr. Opin. Struct. Biol. 3 (1993), 572-579, a paper by Hoess; Curr. Opin. Struct. Biol. 2 (1992), 597-604, a paper by Wells and Lowman; or the “colony screening” method (Anal. Biochem. 196 (1991), a paper by Skerra et al. Published in 151-155); Display "(for example, a paper by Roberts published in Curr. Opin. Chem. Biol. 3 (1999), 268-273). The complex formation between these VEGF antibodies that actually bind to VEGF can then be detected by a change in the conductivity of the nanowire sensor.

  FIG. 26B shows how complex formation (or hybridization when both the capture molecule to be detected and the ligand to be detected is a nucleic acid) is detected by a change in the electrical properties of the nanowire. FIG. 26B shows conductivity change boxes corresponding to each of the p-type and n-type silicon nanowire arrays when the sensor to which the nucleic acid molecule of SEQ ID NO: 1 is attached is contacted with the solution containing the DNA molecule of SEQ ID NO: 2. The plot is shown. The change in conductivity is measured in percent (%). The box plot of FIG. 26B shows the change in conductivity for a buffer solution of 1 μM (micromolar) single-stranded DNA (ssDNA) corresponding to each of the p-type and n-type silicon nanowire arrays. A non-biotinylated and negatively charged capture DNA probe acts to increase the conductivity of p-type silicon nanowires and lower the conductivity of n-type silicon nanowires with respect to the conductivity measured in a buffer solution. To do.

  FIG. 27 shows a box plot of the conductivity change corresponding to different concentrations of the probe DNA of SEQ ID NO: 1 attached to the n-type silicon nanowire array. The concentration of probe DNA is measured in nanomolar (nM) units, and the change in conductivity is measured in percent (%). From the box plot, it can be seen that the conductivity of the n-type silicon nanowire array decreases with increasing probe DNA concentration.

  The foregoing descriptions of various embodiments have been made for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and obviously many variations and modifications may be made based on the disclosed teachings. The scope of the invention is defined by the claims appended hereto.

Claims (68)

A method of forming a sensor comprising nanowires on a support substrate, wherein the first semiconductor layer is disposed on the support substrate:
Forming a fin structure comprising the first semiconductor layer, the fin structure including at least two support portions and a fin portion disposed between the support portions;
Forming a nanowire surrounded by the first oxide film layer by oxidizing at least the fin portion of the fin structure;
Forming a first insulating layer on the support, and
The support and the first insulating layer constitute a microfluidic channel;
Method. The method according to claim 1, further comprising forming a second oxide layer on the contact surface of the support before forming the first insulating layer. The method according to claim 1, further comprising forming a first conductive layer on a contact surface of the second oxide film layer before forming the first insulating layer. The method according to any one of claims 1 to 3, further comprising the step of planarizing the first insulating layer. The method of claim 4, wherein the step of planarizing the first insulating layer is performed by a process including one of chemical mechanical planarization, chemical polishing, mechanical polishing, and ion milling. The method further comprises removing a portion of the first insulating layer to form a portion of a microfluidic channel, thereby enabling processing of the contact surface of the first oxide layer surrounding the nanowire. Item 6. The method according to any one of Items 1 to 5. The method according to claim 6, wherein a part of the first insulating layer is removed by dry etching. The method according to claim 1, further comprising removing the first oxide layer surrounding the nanowires to expose the nanowires. The method according to claim 8, wherein the removal of the first oxide film layer surrounding the nanowire is performed by wet etching. 10. A method according to any one of the preceding claims, further comprising the step of closing the microfluidic channel with a cap layer. The method according to claim 1, further comprising doping the fin portion with at least one dopant. The method of claim 11, wherein the at least one dopant is either p-type or n-type. The method of claim 12, wherein the p-type dopant is one or more elements selected from the group consisting of boron, aluminum, gallium, and indium. The method of claim 12, wherein the n-type dopant is one or more elements selected from the group consisting of phosphorus and arsenic. The method according to claim 1, further comprising forming a gap in the nanowire by removing a part of the nanowire. The method according to claim 15, wherein the removal of a part of the nanowire is performed by selective etching. The method according to claim 1, further comprising the step of coating a part of the nanowire with a dielectric material. The method of claim 17, further comprising performing a silicidation process on the nanowires. The steps of performing the silicidation process are:
Forming a second conductive layer on the nanowire;
Performing a chemical reaction between the nanowire and the second conductive layer by performing a first heat treatment to silicide the nanowire;
Removing the remaining second conductive layer;
The method of claim 18 comprising: The method of claim 19, wherein the second conductive layer comprises a metal or metal alloy. 21. The method according to any one of claims 1 to 20, wherein a second insulating layer is disposed between the support substrate and the first semiconductor layer. The method of claim 21, wherein the second insulating layer comprises a material selected from the group consisting of silicon oxide, polymer, and dielectric material. 23. A method according to any one of the preceding claims, wherein the support substrate comprises a material selected from the group consisting of silicon, sapphire, polysilicon, silicon oxide and silicon nitride. 24. The method of any one of claims 1 to 23, wherein the first semiconductor layer comprises a material selected from the group consisting of silicon, gallium arsenide, and silicon-germanium. 25. A method according to any one of the preceding claims, wherein the nanowire comprises or is made from silicon. 26. A method according to any one of claims 1 to 25, wherein the step of oxidizing at least the fin portion of the fin structure is performed by a self-limiting oxidation process. 27. A method according to any one of claims 1 to 26, wherein the first oxide layer is the same as the second oxide layer. 28. A method according to any one of claims 1 to 27, wherein the first oxide layer is silicon oxide. The method according to any one of claims 1 to 28, wherein the second oxide layer is silicon oxide. 30. The method of any one of claims 1 to 29, wherein the first conductive layer comprises a metal or metal alloy. 31. A method according to any one of claims 1 to 30, wherein the first insulating layer comprises a material selected from the group consisting of silicon oxide, polymer and dielectric material. The method of claim 10, wherein the cap layer is formed of a material selected from the group consisting of silicon, glass, silica, organic polymer, and polydimethylsiloxane. 33. A method according to claim 10 or 32, further comprising forming at least two openings in the cap layer. 34. The method of claim 33, wherein each opening of the cap layer is located at a predetermined distance away from each support. 35. A method according to claim 33 or 34, further comprising filling each opening with the first conductive layer to form an electrical connection from each opening to the contact surface of the support. 36. The method according to any one of claims 1 to 35, further comprising forming a first oxide layer around the support by oxidizing a fin structure. 37. The method according to any one of claims 1 to 36, further comprising depositing a second semiconductor layer on the support substrate prior to depositing the first semiconductor layer. 38. The method of claim 37, further comprising forming an electrode comprising the second semiconductor layer. 40. The method of claim 38, further comprising depositing a third insulating layer over the electrode prior to forming a fin structure. 40. A method according to claim 38 or 39, wherein the electrode is located under the nanowire. 41. The method according to any one of claims 3 to 40, further comprising forming a passivation layer on the first conductive layer prior to forming the first insulating layer. 42. The method of claim 41, wherein the passivation layer comprises a material selected from the group consisting of silicon nitride, silicon oxide, or aluminum oxide. 43. A method according to any one of claims 37 to 42, wherein the second semiconductor layer comprises a material selected from the group consisting of silicon, gallium arsenide and silicon-germanium. 44. A method according to any one of claims 39 to 43, wherein the third insulating layer comprises a material selected from the group consisting of silicon oxide and a dielectric material. A support substrate;
A semiconductor fin structure disposed on the support substrate, the semiconductor fin structure including at least two semiconductor support portions and nanowires disposed between the support portions;
A first insulating layer on a contact surface of the support portion,
The support and the first insulating layer constitute a microfluidic channel;
Nanowire sensor. 46. The nanowire sensor according to claim 45, further comprising a first oxide film layer on the contact surface of the support portion and between the contact surface of the support portion and the insulating layer. 47. The nanowire sensor according to claim 46, further comprising a first conductive layer on the contact surface of the first oxide film layer and between the contact surface of the first oxide film layer and the insulating layer. 48. The nanowire sensor according to any one of claims 45 to 47, wherein the nanowire is located on the support substrate. 49. The nanowire sensor according to any one of claims 45 to 48, wherein the nanowire is composed of an n-type dopant or a p-type dopant. 49. A nanowire sensor according to any one of claims 45 to 48, wherein the nanowire is formed as a P / N diode junction. 51. The nanowire sensor according to any one of claims 45 to 50, wherein the nanowire includes a gap. 52. The nanowire sensor according to any one of claims 45 to 51, wherein the nanowire is silicided. 53. A nanowire sensor according to any one of claims 45 to 52, wherein at least a surface of the nanowire is adapted to constrain a biopolymer. 54. A nanowire sensor according to any one of claims 45 to 53, further comprising a cap layer on the insulating layer that closes the microfluidic channel. 55. The nanowire sensor of claim 54, wherein the cap layer includes at least two openings, each opening being located at a predetermined distance away from each support. 56. The nanowire sensor according to any one of claims 45 to 55, further comprising a second insulating layer disposed between the support substrate and the semiconductor fin structure. 57. The nanowire sensor according to any one of claims 47 to 56, further comprising a passivation layer on the first conductive layer and between the first conductive layer and the first insulating layer. 58. The nanowire sensor according to any one of claims 45 to 57, further comprising an electrode located under the nanowire and between the support substrate and the nanowire. 59. The nanowire sensor of claim 58, further comprising a third insulating layer disposed between the electrode and the nanowire. A plurality of nanowire sensors according to any one of claims 45 to 59,
Each nanowire sensor can be individually specified via the support,
Nanowire sensor array. 61. The nanowire sensor array of claim 60 further comprising a plurality of microfluidic channels. 62. The nanowire sensor array according to claim 60 or 61, further comprising a control unit that individually designates each nanowire sensor. 63. A nanowire sensor array according to any one of claims 60 to 62, wherein one nanowire sensor is used as a reference and another nanowire sensor is used for measurement. 64. A detection method using a nanowire sensor array according to any one of claims 60 to 63, wherein one method uses one nanowire sensor as a reference and another nanowire sensor for measurement. how to. A method for detecting an analyte, the method comprising:
Measuring the first electrical signal of the nanowire sensor according to any one of claims 45 to 63;
Contacting the nanowire sensor with a sample suspected of containing an analyte of interest to fix the analyte to the nanowire;
Measuring the second electrical signal of the nanowire and comparing the measured first electrical signal with the second electrical signal to detect the presence or absence of the specimen;
Including a method. Providing a capture molecule that binds to the analyte on the surface of the nanowire;
66. The method of claim 65, further comprising contacting a sample suspected of containing an analyte of interest with the capture molecule to allow complex formation between the analyte and the capture molecule. . 67. A method according to claim 65 or 66, wherein the presence of an analyte is detected if the difference between the first electrical signal and the second electrical signal exceeds a threshold. 68. The method according to any one of claims 65 to 67, wherein the specimen is a biopolymer, a living organism, or a small organic molecule.